Cytotoxic response of breast cancer cell lines, MCF 7 and T 47 D to triphala and its modification by antioxidants
Cytotoxic response of breast cancer cell lines, MCF 7 and T 47 D to triphala and its modification by antioxidants
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DOI：
10.1016/j.canlet.2005.07.013
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发表时间：
2006-07-18
期刊：
影响因子：
9.7
通讯作者：
Mishra, K. P.
中科院分区：
文献类型：
--
作者：
Sandhya, T.;Mishra, K. P.
Triphala (TPL) 是一种具有已知抗癌特性的印度阿育吠陀配方，已在两种 p53 状态不同的人类乳腺癌细胞系中研究了其细胞毒性作用。体外研究表明，具有野生型 p53 的 MCF 7 对 TPL 比 p53 阴性的 T 47 D 更敏感。通过MTT测定测定TPL诱导的细胞活力丧失。孵育72小时后，发现MCF 7 的IC 50 值类似于8μg/ml，而T 47 D 的IC 50 值类似于26μg/ml。此外，TPL 抑制 MCF 7 细胞的克隆生长，p53 抑制剂 Pifithrin-α 可以显着恢复这种生长。然而，pifithrin-alpha 并没有改变 TPL 在 T 47 D 细胞中诱导的细胞毒性。外源添加抗氧化剂谷胱甘肽（GSH）和N-乙酰半胱氨酸（NAC）抑制了MCF 7和T47 D中TPL的抗增殖能力。对TPL处理的细胞进行Annexin-V和碘化丙啶双染色2次结果显示，TPL以剂量依赖性方式诱导两种细胞系显着凋亡，但MCF 7中的凋亡程度显着高于T 47-D细胞。还发现 TPL 可以诱导两种细胞系中细胞内活性氧的剂量和时间依赖性增加。目前的结果表明，MCF 7 和 T 47 D 细胞对 TPL 表现出不同的敏感性，这似乎取决于它们的 p53 状态。抗氧化剂对 TPL 抗增殖能力的抑制表明 TPL 诱导的 ROS 在诱导细胞凋亡中发挥作用。结论是，癌细胞的p53状态是预测癌细胞对促氧化剂药物反应的重要因素。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
The cytotoxic effects of Triphala (TPL), an Indian Ayurvedic formulation with known anti-cancer properties, has been investigated on two human breast cancer cell lines differing in their p53 status. In vitro studies showed that MCF 7 with wild type p53 was more sensitive to TPL than T 47 D, which is p53 negative. TPL induced loss of cell viability was determined by MTT assay. After 72 h incubation, the IC 50 values for MCF 7 was found to be similar to 8 mu g/ml and that for T 47 D was similar to 26 mu g/ml. Moreover, TPL inhibited the clonogenic growth of MCF 7 cells, which was significantly recovered by pifithrin-alpha, the p53 inhibitor. However, pifithrin-alpha, did not modify TPL induced cytotoxicity in T 47 D cells. Exogenous addition of antioxidants, glutathione (GSH) and N-Acetyl-Cysteine (NAC) inhibited the anti-proliferative ability of TPL in both MCF 7 and T47 D. Annexin-V and propidium iodide double staining of cells treated with TPL for 2 It revealed that TPL induced significant apoptosis in both the cell lines in a dose dependant manner but magnitude of apoptosis was significantly higher in MCF 7 than in T 47-D cells. TPL was also found to induce dose and time dependent increase in intracellular reactive oxygen species in both the cell lines. Present results have demonstrated that MCF 7 and T 47 D cells exhibited differential sensitivity to TPL, which seems to be dependant on their p53 status. Inhibition of anti-proliferative ability of TPL by antioxidants suggests a role for TPL induced ROS in the induction of apoptosis. It is concluded that p53 status of cancer cells formed an important factor in predicting the response of cancer cells to prooxidant drugs. (c) 2005 Elsevier Ireland Ltd. All rights reserved.